Menthyl lactate (ML), an ester of menthol and lactic acid, is a physiological cooling agent widely used in flavors, oral care, and cosmetics. Recently, ML was proposed for cancer treatment or as a diagnostic agent (see, e.g., U.S. Pat. Appl. Publ. 2005/0054651). Because ML has four chiral centers, there are sixteen possible stereoisomers. The most common ML isomer, 1, derives from l-menthol and L(+)-lactic acid:

Few synthetic routes to ML have been reported. One general approach involves asymmetric reduction of menthyl pyruvate (see, e.g., Nishiyama et al., J. Chem. Soc. Chem. Commun. (1976) 101 and Ojima et al., J. Org. Chem. 42 (1977) 1671. This approach uses sophisticated chiral reagents and gives ML in modest chemical and optical yields.
The simplest way to make ML is direct esterification of lactic acid with menthol. Surprisingly few details about this method are available in the literature, however. A century ago, McKenzie et al. (J. Chem. Soc. 87 (1905) 1016) described the preparation of l-menthyl-dl-lactate by esterification from l-menthol and dl-lactic acid “by the hydrogen chloride method.” This appears to involve bubbling hydrogen chloride gas into an ether solution containing l-menthol and an excess amount of dl-lactic acid, followed by washing the ether phase with aqueous sodium carbonate and water, followed by drying, concentration, and distillation. McKenzie observed changes in optical activity when optically active menthyl or bornyl esters (including ML) were hydrolyzed with alcoholic potassium hydroxide at elevated temperature to give the corresponding carboxylic acid salts. The conditions used were not effective to minimize hydrolysis of menthyl lactate; in fact, they were designed to produce menthol and lactic acid by hydrolyzing ML.
Kuhn et al. (U.S. Pat. No. 5,783,725) teach an acid-catalyzed esterification of L(+)-lactic acid and l-menthol. The recommended acids are sulfuric acid, phosphoric acid, methanesulfonic acid, p-toluenesulfonic acid, acid clays, and acidic ion-exchange resins. After a typical workup, the ML product is distilled to 97–98% purity. The reference provides few synthetic details and is silent about the yield of ML obtained.
Direct esterification is also taught by L. Horner et al. (Liebigs Ann. Chem. (1979) 1232). L(+)-Lactic acid and l-menthol are esterified in the presence of chloroform and a strongly acidic ion-exchange resin. After elution with chloroform through a column of alumina and solvent removal, the residue is fractionally distilled to provide a 39% yield of ML.
An improved way to make menthyl lactate is needed. A desirable process would avoid expensive reagents; instead, it would retain the convenience and simplicity of direct esterification. Ideally, the process would be simple to practice and would provide high yields of ML